1. Field of the Invention
This invention relates to a method and device for measuring and processing light in which organisms previously injected with a hematoporphyrin derivative (hereinafter abbreviated as HPD) or other fluorescent substances which have a strong affinity for tumors are irradiated with laser light at predetermined positions such as the trachea, bladder, etc. in order to produce fluorescent light, and tumors in them are diagnosed by means of the intensity of the fluorescence produced at this time and by the intensity of the reflected light, or in which they are given therapy by irradiation with laser light of another wavelength.
2. Description of the Prior Art
Methods and devices for cancer diagnosis and therapy utilizing the photochemical reactions between laser light and fluorescent substances such as HPD which have a strong affinity for tumors have been proposed (Japanese Patent Application Disclosures Nos. SHO 59-40830 and SHO 59-40869, U.S. Pat. No. 4,556,057).
FIG. 1 is a block drawing illustrating the basic configuration of the diagnostic device of the past.
It can be divided, insofar as the configuration of the device is concerned, into an ordinary endoscopic diagnostic system 17 and a photochemical reaction diagnostic therapeutic system 18. In FIG. 1, a fiber bunch 15 is incorporated in the endoscope and is inserted into the patient's body at the position suspected to be the focus, the patient having been previously given an intravenous injection of HPD.
The endoscopic diagnostic system 17 consists of a white light source 7 for illuminating a tissue surface 1, a light guide 3 conducting this light, an image guide 2 conducting images of the tissue surface 1 to a color camera 6, and a monitor TV 13 for displaying images of the tissue surface 1 picked up by the color camera 6.
The photochemical reaction diagnostic/therapeutic system 18 is equipped with a laser light source 8 which outputs, as pulsed laser light, both laser light for diagnosis (405 nm) and laser light for therapy (630 nm).
The laser light for diagnosis is conducted to the affected part by means of a light guide 4. It is irradiated onto the affected part and excites fluorescence.
The fluorescence produced by the exciting light is conducted by a light guide 5 to a spectroscope 9.
Fluorescence spectrum images 10 obtained from the spectroscope 9 are picked up by a high-sensitivity camera 11, video signals 16 output by it are converted into graphic images by arithmetical processing in an analytical circuit 12, and the images are displayed on a monitor TV 14 as spectrum patterns. The spectrum images 10 are set within the wavelength region of 600-700 nm so that it will be possible to observe the spectrum with two peaks at 630 nm and 690 nm which is a characteristic of HPD fluorescence.
Since endoscopic diagnosis and photochemical reaction diagnosis/therapy are carried out concurrently, the white light source 7 and laser light source 8 irradiate the tissue 1 by a timesharing system. The high-sensitivity camera 11 which picks up the fluorescence spectrum operates intermittently, synchronized with the irradiation of laser light.
Using this device, the operator during diagnosis can locate a cancer while viewing at the same time the tissue images on the monitor TV 13 and the fluorescence spectrum patterns on the monitor TV 14. If a cancer is discovered, the operator can perform therapy immediately by merely switching over the light from exciting light to therapeutic light.
Therapy is carried out by means of a photochemical reaction between the HPD remaining in the cancerous part and the therapeutic light. This causes necrosis selectively at the cancerous part only.
Furthermore, as for the detection of fluorescence during diagnosis, the spectrum patterns which are unique to the fluorescence themselves are observed directly and are not confused with the spontaneous fluorescence emitted from the normal parts themselves. This makes it possible to determine the presence of cancer easily. This may possibly contribute greatly to the diagnosis and therapy of cancer in the early stage, particularly in cases where it is difficult to discover by means of endoscopic diagnosis alone.
As was described above, this device utilizes the affinity of HPD for tumors in the diagnosis and therapy. In actual fact, diagnosis is performed after waiting for two or more days after injection of the HPD until such time as the difference in concentration of the residual HPD between normal cells and cancerous cells reaches a ratio of about 1:10, the exact time differing somewhat depending upon the organ in which one is interested. Consequently, the detection of fluorescence does not in itself indicate the presence of cancer, and the intensities must be distinguished in order to determine whether or not cancer is present.
Furthermore, when the area of the cancerous part is smaller than the area irradiated with exciting light (the diameter of the latter ordinarily ranges from several mm to 10 mm), even though the concentration ratio of the residual HPD may be 1:10, the differences in the detected intensity of the fluorescence attributable to the presence or absence of cancer will be far smaller.
For example, if we assume that the amount of fluorescence is directly proportional to the HPD concentration, the ratio between the fluorescent intensity when a cancer 1 mm in diameter is present within an irradiated range 5 mm in diameter will become quite close to the fluorescent intensity when such a cancer is absent, the ratio amounting in this case to about 1.36:1.
The following fluctuating factors may also be mentioned as items making this discrimination even more difficult:
(1) Power fluctuations of the laser light
(2) Fluctuations in the relative positions of the irradiating fiber opening and the irradiated surface
(3) Fluctuations in the relative positions of the fluorescent part (the irradiated surface) and the detecting fiber opening
(4) Fluctuations of the effective detection area of the detecting fiber due to shaking of the irradiating fiber (that is, shaking of the irradiating position)
As for factor (1) above, there are instantaneous power fluctuations of about 5-10% in light sources which combine an excimer laser with a dye laser, such as those which were used in the past example mentioned above.
Factors (2)-(4) are fluctuations due to manipulation of the endoscope. On account of factor (2), the density of the exciting light irradiated onto the tissues varies in inverse proportion to the square of the distance.
On account of factor (3), of the fluorescence produced, the percentage which enters the detecting fiber varies in inverse proportion to the square of the distance. In addition, since the irradiation area and focusing area also vary in accordance with fluctuations of factors (2) and (3), one may assume that factors (2) and (3) taken together will cause the detected intensity of the fluorescence to fluctuate approximately in inverse proportion to the square of the distance.
In factor (4), shaking of the irradiating fiber is caused by the following. That is, deterioration of the irradiating fiber tends to be brought about by the strong pulsed light, ordinarily with a repeated frequency of several tens of hertz and a peak power of about 1 megawatt, which passes through the fiber. A condition for mounting irradiating fiber in an endoscope is that the fiber must be easily replaceable. Thus, inserting the fiber into the forceps opening of the endoscope is the easiest method for mounting and removing it, and this is the method in general use.
However, when this method is used, the aforementioned shaking occurs because of manipulation of the endoscope, particularly when the endoscope is bent, because the irradiating fiber and the endoscope do not form an integrated whole. Discrepancies between the irradiating position and the field of observation of the fluorescence detecting fiber occur as a result. This causes fluctuations of the effective detection area of the fluorescent light, and the detected intensity of the fluorescence also fluctuates.
The fluctuating factors explained above are all superimposed on each other and influence the detected intensity of the fluorescence. This leads to certain problems. For example, stronger fluorescence may be detected from nearby normal cells than from more distant cancerous cells; or, even when the exciting light is irradiated on cancerous cells, its fluorescence may not enter the field of the detecting fiber, and an intense fluorescence spectrum may not be observed at all. These problems make it exceedingly difficult to determine whether or not cancer is present.
In connection with problems of this type, the following is a technology which has been used in controlling items such as the light source for illumination in endoscopes of the past. In this technology, another fiber is used to detect the reflected light of the light irradiated from the light source through the fiber, and the amount of light output from the light source is controlled in accordance with the amount of light detected by this other fiber. Thus, the amount of irradiated light is kept constant.
Nevertheless, the following inconveniences result when an attempt is made to apply this method for resolving the aforementioned problems.
First of all, because of the delay factor which is inherent in the feedback control system, the fluctuating factors cannot be compensated for at every pulse of the irradiated laser light.
Second, it is difficult to control the output of pulsed lasers with a good precision throughout a range amounting to multiples of about 10, and to control it with a time constant approximately equivalent to the blurring of the endoscope.
Third, concerning the aforementioned fluctuating factor (4), when the irradiation position has departed from the field of detection, control will be difficult, and it is also possible that excessive amounts of light will be irradiated. Given the control performance which is required in medical equipment, it would seem to be quite difficult to realize the needed improvements.